Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus.
Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM) and affects about 30% of these patients. We have previously localized a DN locus on chromosome 3q with suggestive linkage in Finnish individuals. Linkage to this region has also...
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Online Access: | https://doi.org/10.1016/j.ajhg.2008.11.012 https://pubmed.ncbi.nlm.nih.gov/19084216 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668055/ |
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ftpubmed:19084216 2024-06-09T07:47:12+00:00 Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. He, Bing Osterholm, Anne-May Hoverfält, Anna Forsblom, Carol Hjörleifsdóttir, Eyrún Edda Nilsson, Ann-Sofie Parkkonen, Maikki Pitkäniemi, Janne Hreidarsson, Astrádur Sarti, Cinzia McKnight, Amy Jayne Maxwell, A Peter Tuomilehto, Jaakko Groop, Per-Henrik Tryggvason, Karl 2009 Jan https://doi.org/10.1016/j.ajhg.2008.11.012 https://pubmed.ncbi.nlm.nih.gov/19084216 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668055/ eng eng Elsevier Science https://doi.org/10.1016/j.ajhg.2008.11.012 https://pubmed.ncbi.nlm.nih.gov/19084216 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668055/ Am J Hum Genet ISSN:1537-6605 Volume:84 Issue:1 Journal Article Research Support, Non-U.S. Gov't 2009 ftpubmed https://doi.org/10.1016/j.ajhg.2008.11.012 2024-05-11T16:02:00Z Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM) and affects about 30% of these patients. We have previously localized a DN locus on chromosome 3q with suggestive linkage in Finnish individuals. Linkage to this region has also been reported earlier by several other groups. To fine map this locus, we conducted a multistage case-control association study in T1DM patients, comprising 1822 cases with nephropathy and 1874 T1DM patients free of nephropathy, from Finland, Iceland, and the British Isles. At the screening stage, we genotyped 3072 tag SNPs, spanning a 28 Mb region, in 234 patients and 215 controls from Finland. SNPs that met the significance threshold of p < 0.01 at this stage were followed up by a series of sample sets. A genetic variant, rs1866813, in the noncoding region at 3q22 was associated with increased risk of DN (overall p = 7.07 x 10(-6), combined odds ratio [OR] of the allele = 1.33). The estimated genotypic ORs of this variant in all Finnish samples suggested a codominant effect, resulting in significant association, with a p value of 4.7 x 10(-5) (OR = 1.38; 95% confidence interval = 1.18-1.62). Additionally, an 11 kb segment flanked by rs62408925 and rs1866813, two strongly correlated variants (r(2) = 0.95), contains three elements highly conserved across multiple species. Independent replication will clarify the role of the associated variants at 3q22 in influencing the risk of DN. Article in Journal/Newspaper Iceland PubMed Central (PMC) The American Journal of Human Genetics 84 1 5 13 |
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Open Polar |
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PubMed Central (PMC) |
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ftpubmed |
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English |
description |
Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM) and affects about 30% of these patients. We have previously localized a DN locus on chromosome 3q with suggestive linkage in Finnish individuals. Linkage to this region has also been reported earlier by several other groups. To fine map this locus, we conducted a multistage case-control association study in T1DM patients, comprising 1822 cases with nephropathy and 1874 T1DM patients free of nephropathy, from Finland, Iceland, and the British Isles. At the screening stage, we genotyped 3072 tag SNPs, spanning a 28 Mb region, in 234 patients and 215 controls from Finland. SNPs that met the significance threshold of p < 0.01 at this stage were followed up by a series of sample sets. A genetic variant, rs1866813, in the noncoding region at 3q22 was associated with increased risk of DN (overall p = 7.07 x 10(-6), combined odds ratio [OR] of the allele = 1.33). The estimated genotypic ORs of this variant in all Finnish samples suggested a codominant effect, resulting in significant association, with a p value of 4.7 x 10(-5) (OR = 1.38; 95% confidence interval = 1.18-1.62). Additionally, an 11 kb segment flanked by rs62408925 and rs1866813, two strongly correlated variants (r(2) = 0.95), contains three elements highly conserved across multiple species. Independent replication will clarify the role of the associated variants at 3q22 in influencing the risk of DN. |
format |
Article in Journal/Newspaper |
author |
He, Bing Osterholm, Anne-May Hoverfält, Anna Forsblom, Carol Hjörleifsdóttir, Eyrún Edda Nilsson, Ann-Sofie Parkkonen, Maikki Pitkäniemi, Janne Hreidarsson, Astrádur Sarti, Cinzia McKnight, Amy Jayne Maxwell, A Peter Tuomilehto, Jaakko Groop, Per-Henrik Tryggvason, Karl |
spellingShingle |
He, Bing Osterholm, Anne-May Hoverfält, Anna Forsblom, Carol Hjörleifsdóttir, Eyrún Edda Nilsson, Ann-Sofie Parkkonen, Maikki Pitkäniemi, Janne Hreidarsson, Astrádur Sarti, Cinzia McKnight, Amy Jayne Maxwell, A Peter Tuomilehto, Jaakko Groop, Per-Henrik Tryggvason, Karl Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. |
author_facet |
He, Bing Osterholm, Anne-May Hoverfält, Anna Forsblom, Carol Hjörleifsdóttir, Eyrún Edda Nilsson, Ann-Sofie Parkkonen, Maikki Pitkäniemi, Janne Hreidarsson, Astrádur Sarti, Cinzia McKnight, Amy Jayne Maxwell, A Peter Tuomilehto, Jaakko Groop, Per-Henrik Tryggvason, Karl |
author_sort |
He, Bing |
title |
Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. |
title_short |
Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. |
title_full |
Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. |
title_fullStr |
Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. |
title_full_unstemmed |
Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. |
title_sort |
association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. |
publisher |
Elsevier Science |
publishDate |
2009 |
url |
https://doi.org/10.1016/j.ajhg.2008.11.012 https://pubmed.ncbi.nlm.nih.gov/19084216 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668055/ |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Am J Hum Genet ISSN:1537-6605 Volume:84 Issue:1 |
op_relation |
https://doi.org/10.1016/j.ajhg.2008.11.012 https://pubmed.ncbi.nlm.nih.gov/19084216 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668055/ |
op_doi |
https://doi.org/10.1016/j.ajhg.2008.11.012 |
container_title |
The American Journal of Human Genetics |
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84 |
container_issue |
1 |
container_start_page |
5 |
op_container_end_page |
13 |
_version_ |
1801378152541323264 |